Stomatitis, an inflammation of the mucous lining of the mouth, is a harmful adverse effect of high or multiple dosing of cytotoxic agents such as 5-fluorouracil. To prevent stomatitis induced by such cancer chemotherapy, oral dosage forms including radical scavenging agents such as allopurinol (APN) or rebamipide have been prepared. In the present study, the pharmaceutical utility of a gel or mouthwash consisting of polyethylene (oxide) (PEO) and carrageenan (κ- CG or ι-CG) was investigated as an oral dosage preparation with the potential for greater ease of handling and swallowing. Examination of the gelation behavior of preparations with a variety of PEO and/or CG concentrations and handling of the gelled material indicated that the optimum gel compositions (PEO : ι-CG % ratio) were 0.5 : 2.0, 1.0 : 2.0 and 2.0 : 2.0. From the results of sensory testing, it was determined that ι-CG was a more suitable gel material because it has no taste or odor, unlike κ-CG which has its own special taste and odor. The release behavior of APN from APN gels was investigated by the paddle-bead method, mimicking the chewing action. The APN gel was effectively sheared by the beads and the release of APN completed within 480 s. The results of sensory testing confirmed that an APN gel containing 2.0 % ι-CG and 1.0 % PEO was the best type as it produced a jelly-like preparation. In the case of mouthwashes, the adhesiveness of the drug was found to increase as the concentration of PEO increased, and the adhesion of a mouthwash containing PEO was greater than one containing sodium carboxymethylcellulose (CMC-Na). When APN was dissolved in a mixture of PEO-ι-CG and sprayed onto the oral mucosa, the preventive effect against stomatitis was greater than that of a mouthwash containing APN and CMC-Na. The results obtained in this study indicate that a mixture of PEO and ι-CG may be a useful new dosage form for improving patient adherence to medication.

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Stroke is the third most common cause of death in Japan. Although significant breakthroughs have been made in the development of advanced drugs, the necessity for using them in a limited time window and adverse effects can restrict their application, making it still necessary to explore new therapeutic targets and strategies.
It is well known that hyperglycemia can exacerbate ischemic neuronal damage. Also, it has been recently reported that hyperglycemia/glucose intolerance can be induced by cerebral ischemic stress per se, and a clinical study showed that normalization of blood glucose levels during the first 48 h of hospitalization appears to confer a potent survival benefit in patients with thromboembolic stroke. It is therefore important to strictly control blood glucose levels immediately after ischemic stress for neruroprotection. However, the detailed mechanism of post-ischemic glucose intolerance is unknown.
Here, we review the progress in research on the mechanism of the development of post-ischemic glucose intolerance focusing on insulin signaling, adiponectin signaling and communication between the brain and peripheral tissues. Furthermore, from the therapeutic viewpoint, we discuss the effect of anti-diabetic drugs, such as insulin, metformin, and the glucose-sensing neuropeptide orexin-A, on the development of post-ischemic glucose intolerance and additional neuronal damage. In our conclusion, we emphasize the importance of focusing on the development of post-ischemic glucose intolerance as a new therapeutic target of stroke.

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Conventional formulations of pirarubicin hydrochloride for injection dissolve rapidly in water for injection and 5 % glucose injection but they are not very soluble in saline. Therefore, medical practitioners in hospitals have desired a new formulation of pirarubicin hydrochloride for injection that dissolves readily in saline. In view of this, we conduced an investigation of solubilizers and found that pirarubicin hydrochloride dissolved rapidly in saline when nicotinamide was added, and developed a formulation of pirarubicin hydrochloride for injection containing 25 mg of nicotinamide per 20 mg potency of pirarubicin hydrochloride.
¹H-NMR spectrum analyses revealed that self-association of pirarubicin molecules occurred in saline. The results of such analyses suggested that pirarubicin hydrochloride rapidly dissolved when nicotinamide was added because it inhibited the selfassociation of pirarubicin molecules by preventing interaction between them. As other findings, the chemical stability and in vitro pharmacological effect of the new formulation of pirarubicin hydrochloride for injection as well as its pharmacokinetics in rats were similar to conventional formulations, and nicotinamide did not provide a local stimulus to the rabbit bladder.

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Cancerous malodor remarkably decreases the quality of life of patients. However, in the absence of a standard topical therapy for it, we have to use a hospital preparation.
We report the case of a patient with extensive malodorous malignant effusion who was successfully treated with clindamycin-pate. The patient was a 49-year-old man who had malignant melanoma. The melanoma had spread to the intracranial region and left axillary and para-aortic lymph nodes. The metastatic lesion in the left axillary lymph node released a strong odor. Cadexomer-iodine ointment was first used for treatment of the lesion but was ineffective against the effluvium so we changed it to clindamycin-pate.
In a survey of hospital staff, 87.5% stated that the foul smell had disappeared after treating the patient with clindamycin-pate. Clindamycin-pate has been seen to exhibit significant antimicrobial activity against gram-positive and anaerobic bacteria and this is probably the reason for its effectiveness against the foul smell. It also absorbed a considerable amount of the effusion, eliminating the need to use carboxymethylcellulose sodium salt (CMC-Na). Therefore, clindamycin-pate is considered to be an effective adjuvant therapy for controlling malodorous effusion in cancer patients. Furthermore, in a comparison of hydrophilia with various external preparations, clindamycin-pate was found to have remarkable moisture absorption capability, providing further evidence of its usefulness in the control of effusions.

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With the inclusion of a fee for providing drug information in the medical fee charging structure in 1996, the provision of information on drug information leaflets (hereinafter simply called “leaflets”) became more prominent. However, as some patients have said they do not read leaflets or they do not need them, we felt that the drug information provided on leaflets should be reevaluated to have it better reflect the fee charged.
To do this, we conducted a survey of patients (n=195, age: 17-93 year) on their usage of leaflets. Almost all of the patients read leaflets and kept them. We also found that patients had a keen sense of the necessity of leaflets and were satisfied with them. In addition, level of need for leaflets and opinions on the way information should be provided on them varied with age group.
Therefore, in the future, we should focus not only on the content of the drug information but also on using ways of providing drug information that meet the needs of different patients. We feel that that this will lead to more effective provision of drug information to patients and help ensure the proper use of medicines.

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The inter- and intra-trial variability of maximum plasma concentration, a pharmacokinetics parameter of standard products, was investigated for various generic products (GEs) in biological equivalence clinical studies. A correlation between such variability and the typical physical properties of the GEs was also investigated. The product with the maximum inter-trial variability was an ethyl icosapentate GE, and that with the minimum variability was a theophylline one. The average value of the coefficient of inter-trial variation (CVc) of all the investigated GEs was 24.6±1.8% (mean ± standard error). In addition, there was significant positive correlation between CVc and LogP, a lipophilic parameter. This suggests that the absorption of medicines with high lipophilicity was greatly influenced by the intestinal condition factors of subjects, such as the elapsed time after a meal, the content of the meal and volume of water drunk with the medicine; which caused the inter-trial variability.
On the other hand, intra-trial variability was high for medicines that were substrates of metabolic enzymes and/or transporters with genetic polymorphism and it was thought that this was a major reason for the individual pharmacokinetic differences of these medicines.

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Paclitaxel injection [NK] (PTX [NK]) is a generic of Taxol^® Injection (Taxol) but no non-clinical study comparing the safety of the 2 drugs has been conducted because the active ingredient is the same.
We compared the safety of PTX [NK] and Taxol in rats to see if there were any differences. PTX [NK] and Taxol were intravenously administered to CD (SD) male rats at doses of 2.0 and 4.0 mg/kg/day for 9 days. There were very slight differences in toxicological findings regarding such items as clinical observations, food consumption, gross necropsy, organ weight and histopathology. These differences, however, were generally observed after administration of a cytocidal anticancer drug. Therefore, such differences were not thought to be toxicologically significant and we concluded that the safety of PTX [NK] was no different from that of Taxol in rats.

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Pharmacists working in community pharmacies must provide consultation to cancer patients in order to ensure the safety of medical care. However, they only have access to patients' prescription information and cannot check whether patients have given informed consent or not. In this empirical study, we analyzed the current status of communication between cancer patients and community pharmacists. A total of 11 pharmacists in Aichi prefecture agreed to participate. They were interviewed and informed about the oral medication for a simulated cancer patient. The conversations during interviews were analyzed using the Roter Method of Interaction Process Analysis System (RIAS). We also picked out phrases that were deemed unsuitable for communication with patients as an indicator of whether there were any problems in the approach of pharmacists to patients.
Our findings were as follows: 1) Even though pharmacists focused on having a good relationship with cancer patients when explaining medications, patient-centered communication was not achieved because patients only listened passively to the explanations; 2) community pharmacists had difficulty in fulfilling their role as a partner in medical care because they were generally unable to gain information on the cancer patient's disease, treatment or psychological state; 3) On average, pharmacists obtained 50.7% of the information on the patient's problems and in some cases, they lacked the communication skills necessary for obtaining information on patient backgrounds or used unsuitable phrases when speaking to them; 4) Pharmacies do not appear to be an appropriate environment for informing patients concerning their medications.
It is therefore necessary to develop a training program that will improve pharmacists'skills in communicating with cancer patients.

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